The objectives of this proposal are to establish the effects on the offspring of diazepam therapy in stressed and unstressed pregnant rats. Diazepam is one of the most widely prescribed drugs and has been used for a variety of reasons in obstretric practice. Yet there is little definitive information concerning the effects on the offspring of prenatal exposure to the drug. Restraint stress of rats during the third week of gestation induces long-term neurochemical and behavioral changes in the offspring. Our initial studies on the effects of prenatal exposure to diazepam during the third week of pregnancy in the rat, demonstrated marked effects on the growth and behavioral development of the offspring. The research proposed will address the question of whether diazepam therapy to the stressed dam can prevent stress-induced changes in the offspring or whether the effects of stress will influence the response in the offspring to diazepam. The mediation of stress responses and the action of diazepam appear to involve similar central mechanisms and an interaction between the two manipulations is possible. This study will identify particulr effects of stress and/or diazepam exposure (13-20 days of gestation) in neonates and adult offspring. Behavioral studies will involve analysis of the development of locomotor activity and the acoustic startle reflex as well as analysis of adult male sexual behavior. Neurochemical studies will examine the effect of the manipulaions on the development of benzodiazepine binding, GABA neurons, and norepinephrine neurons. The pharmacokinetic studies are designed to correlate actual drug levels and the distribution of diazepam and its metabolites with the behavioral and neurochemical changes.